Endocytosis is a general term defining processes, by which a cell imports selected extracellular species, such as molecules, viruses, particles and microorganisms and target them to specific organelles within a cytoplasm. Particle endocytosis can be of fundamental importance in several applications including drug and gene delivery and nanotoxicology, see e.g. Vasir J. K., Labhasetwar V., Expert Opin. Drug Deliv. 2006; 3(3):325-44, and Oberdorster G., et al., Environ. Health Perspect. 2005; 113(7):823-39. Endocytosis can occur through a variety of pathways including clathrin-dependent and independent receptor-mediated endocytosis, pinocytosis and phagocytosis.
A receptor-mediated endocytosis (RME) is an effective mechanism for cellular uptake of micrometric and sub-micrometric particles that have grafted or non-specifically adsorbed on their surfaces molecules, such as ligands, that are capable of binding specifically to countermolecules, such as receptors, expressed on the cell's membrane. The receptors can enter the cell by membrane invagination together with the particles. During the RME, the receptors expressed over the cell membrane can be collected at the site of invagination by surface diffusion, a process without which endocytosis would not occur or would have occurred over a much longer time scale. A detailed review of different endocytotic mechanisms and features can be found, for example, in Mukherjee S., et al. Physiol. Rev. July 1997; 77(3):759-803.
Gao, Shi and Freund proposed a mathematical model for the receptor-mediated endocytosis of particles, see Gao H., Shi W., Freund L. B., Proc. Natl. Acad. Sci. USA, 2005 5; 102(27):9469-74, 2005, which showed that a threshold particle radius may exist, below which endocytosis is not energetically favorable; and an optimal particle radius may exist, slightly larger than the threshold radius, for which a characteristic time for particle wrapping is minimized. Consequently, it was speculated that particles with a size smaller than the threshold radius can never be internalized by receptor mediated endocytosis, whereas particles with a size equal to the optimal particle radius are the fastest to be internalized. The work of Gao and colleagues, however, suffers from at least one drawback: it does not take into account non-specific interactions that arise on the cell-particle interface. There is continuing interest in the development of ways to enhance endocytosis of specified particles into cells.